1. Field of the Invention
The present invention relates to a microdosing apparatus, to methods for dosed dispensing of liquids and to methods for adjusting a desired dosing volume range when using an inventive microdosing apparatus.
2. Description of the Related Art
According to the prior art, volumes in the nanoliter range (10−12 m3) are not dosed with conventional pipettes, but require specific methods to ensure the required precision.
Here, in addition to contact methods, conventional dispensing methods, pin printing methods, etc., contactless methods are of significant importance.
A class of known methods is based on fast-switching valves. Therefore, a suitable valve, mostly based on magnetic or piezoelectrical drives, is connected to a media reservoir via a conduit and pressure is built up in the same. By the fast switching of the valve with a switching time of less than 1 ms, a very large flow is generated for a short term, so that the fluid, even with high surface tensions, can separate from the dispensing position and can impinge on the substrate as free jet. The dosing amount can be controlled by the pressure and/or the switching time of the valve.
Different approaches exist for generating the pressure, there are in the above-described concept with switched valves.
A schematic representation showing a first known approach, which can be referred to as syringe solenoid method, is shown in FIG. 7. Here, a fluid conduit 10 is fluidically connected to a syringe 14, which can be removable, via a fast-switching microsolenoid valve 12. At the lower end of the syringe 14, there is a nozzle opening 16. The opposite end of the fluid conduit 10 is connected to a syringe pump 20 via a switching valve 18. Further, a fluid reservoir 22 is also connected to the switching valve 18 via a further fluid conduit 24.
The switching valve 18 has two switching states. In a first switching state, a pump chamber 26 of the syringe pump 20 is fluidically connected to the fluid reservoir 22 via the fluid conduit 24, so that liquid 28 can be drawn from the fluid reservoir into the pump chamber 26, by increasing the volume of the pump chamber 26 by a corresponding movement of the piston 30 of the syringe pump. This process serves to fill the syringe pump 20. In a subsequent dosing process, the switching valve 18 is switched to effect a fluidic connection of the pump chamber 26 to the microsolenoid valve 12 via the fluid conduit 10. By using the piston 30, pressure is applied to the liquid inside the pump chamber 26, so that by fast switching the microsolenoid valve 12 (switching time <1 ms), liquid can be dispensed from the dosing opening 18 of the syringe 14. Dosing apparatuses of the type shown in FIG. 7 are, for example, sold by the company Cartesian.
An alternative principle, as is practiced, for example, by the companies Delo and Vermes, is shown in FIG. 8. In this alternative method, a pressure container 40 is provided, containing liquid 42 under pressure. An outlet of the pressure container 40 is connected to a quickly switchable valve 46 via a fluid conduit 44, which is again connected to a nozzle opening, shown merely schematically as arrow in FIG. 8, via a fluid conduit 48. In this arrangement, liquid can also be dispensed in a free jet from the nozzle opening by fast switching of the valve 46.
Alternative known microdosing apparatuses are, for example, described in DE-A-19802367, DE-A-19802368 and EP-A-0725267. The microdosing apparatuses described there comprise a pump chamber abutting to a flexible membrane and connected to a reservoir via a supply line and to a nozzle opening via a drain. An example for such a microdosing apparatus will be discussed below with reference to FIGS. 9a-9c. 
In FIG. 9a, a schematic cross section through such a microdosing apparatus in the resting position is shown. The dosing apparatus comprises a dosing head 50 and an actuating device 52. In the shown example, the dosing head 50 is formed by two interconnected substrates 54, 56, in which respective recesses are formed. The first substrate 54 is structured such that a reservoir connection 58, an inlet channel 60 and a dosing chamber 62 are formed in the same. The lower substrate 56 is structured such that a nozzle connection 64, a nozzle 66 having a nozzle channel and an outlet opening, and an outlet area 68 having a significantly larger cross section than the outlet opening of the nozzle 66 are formed in the same.
Further, a membrane 70 is formed the upper substrate 54 by the structuring of the same.
The actuating device 52 has a displacer 72, by which the membrane 70 can be deflected downwards to reduce the volume of the dosing chamber 62, as shown in FIG. 9b. By this reduction of the volume of the dosing chamber 72, on the one hand, a backflow 74 results through the inlet channel 60 and the reservoir connection 58. On the other hand, a forward flow results through the nozzle connection 64 and the nozzle 66, so that dispensing liquid 76 takes place at the outlet end of the nozzle 66. The ratio between backflow 74 and dosed liquid 76 depends on the ratio of flow resistance of fluid connection between reservoir and dosing chamber to the flow resistance between dosing chamber and outlet opening of the nozzle 66.
After the dosing process, the displacer 72 is moved upwards by using the actuating device 52, see FIG. 9c, so that the same finally resumes its original position by elasticity, as shown in FIG. 9a. By this resetting of the membrane 70, an increase of the volume of the dosing chamber 62 results, so that a refill flow 78 from the reservoir through the reservoir connection 58 and the inlet channel 60 occurs. In order to avoid an intake of air through the nozzle 66 during this phase, resetting the membrane 70 has to be performed slowly enough, so that capillary forces keeping the liquid in nozzle 66 are not overcome thereby.
Microdosing apparatuses as described above with reference to FIGS. 9a-9c have originally been developed for enzyme dosage in biochemistry. By using these apparatuses, liquids with viscosities up to 100 mPas in a volume range of 1 nL to 1000 nL can be dosed very media independent and precisely. The liquid to be dosed is thereby dosed by displacing a dosing chip, preferably made of silicon, in free jet from the dosing chamber, which is. However, this method requires a comparatively complex micro device.
Finally, a droplet ejection system is known from U.S. Pat. No. 3,683,212, wherein a tube shaped piezoconverter connects a fluid conduit to a nozzle plate wherein a nozzle opening is formed. A voltage pulse with short rise time is applied to the converter to effect contraction of the converter. The resulting sudden decrease of the enclosed volume causes a small amount of fluid to be ejected from the opening in the opening plate. Thereby, the liquid is kept under no or no low pressure. The surface tension at the opening prevents that liquid flows out when the converter is not operated.
The ejected liquid is replaced by a capillary forward flow of liquid in the conduit.
It has been found out that according to U.S. Pat. No. 3,683,212, the drop is generated with the help of an acoustic principle similar to the piezoelectric inkjet methods. Here, an acoustic pressure wave is generated in a rigid fluid conduit, for example a rigid glass capillary, which results in a high pressure gradient locally at an output position, which leads to drop separation. The actuating time of the actuator is here in the range of the sound propagation in the system, which is normally several microseconds. Thus, in this context, the acoustic impedance of the fluid conduits below and above the actuator is of significance for the design. Thus, this is an impulse method where a high acoustic impulse is generated with a low volume displacement. In other words, a sound wave with pressure maxima and pressure minima is generated between the actuation position and the disposing position, wherein ejection of liquid is effected at the dispensing position by a corresponding pressure. According to U.S. Pat. No. 3,683,212, the fluid conduit is only negligibly deformed, the actuator mainly only transmits sound and the elasticity of the fluid conduit has no significant importance.
From DE 4314343 C2, an apparatus for dosing liquids is known, having a liquid supply tube connected at one end to a liquid reservoir and open at the other end. The tube is applied to an abutment socket and a hammer is provided on the side opposing the abutment socket of the tube. The hammer can vibrated periodically in a direction transversal to the tube axis, so that the whole tube cross section is crimped by the hammer, i.e. the flow area is substantially brought to zero. Thereby, impulsive force impacts are exerted on the tube and individual liquid drops are driven out of the open end.